Type

Journal Article

Authors

Peter Andersen
Joseph Cassidy
Erik Michael Rasmussen
Jonathan Filskov
Thomas Lindenstrøm
Ida Rosenkrands
Sugata Roy
Jes Dietrich

Subjects

Microbiology

Topics
tumor necrosis factor alpha interferon alpha pathology immune system adaptive immunity interferon ifn mycobacterium tuberculosis cd4 t cells

Differential Influence of Nutrient-Starved Mycobacterium tuberculosis on Adaptive Immunity Results in Progressive Tuberculosis Disease and Pathology. (2015)

Abstract When infected with Mycobacterium tuberculosis, most individuals will remain clinically healthy but latently infected. Latent infection has been proposed to partially involve M. tuberculosis in a nonreplicating stage, which therefore represents an M. tuberculosis phenotype that the immune system most likely will encounter during latency. It is therefore relevant to examine how this particular nonreplicating form of M. tuberculosis interacts with the host immune system. To study this, we first induced a state of nonreplication through prolonged nutrient starvation of M. tuberculosis in vitro. This resulted in nonreplicating persistence even after prolonged culture in phosphate-buffered saline. Infection with either exponentially growing M. tuberculosis or nutrient-starved M. tuberculosis resulted in similar lung CFU levels in the first phase of the infection. However, between week 3 and 6 postinfection, there was a very pronounced increase in bacterial levels and associated lung pathology in nutrient-starved-M. tuberculosis-infected mice. This was associated with a shift from CD4 T cells that coexpressed gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) or IFN-γ, TNF-α, and interleukin-2 to T cells that only expressed IFN-γ. Thus, nonreplicating M. tuberculosis induced through nutrient starvation promotes a bacterial form that is genetically identical to exponentially growing M. tuberculosis yet characterized by a differential impact on the immune system that may be involved in undermining host antimycobacterial immunity and facilitate increased pathology and transmission.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Peter Andersen, Joseph Cassidy, Erik Michael Rasmussen, Jonathan Filskov, Thomas Lindenstrøm, Ida Rosenkrands, Sugata Roy, Jes Dietrich

Experts in our system

1
Peter Andersen
University College Dublin
Total Publications: 6
 
2
Joseph P. Cassidy
University College Dublin
Total Publications: 55
 
3
Jes Dietrich
University College Dublin
Total Publications: 3